Novel insights into how purines regulate pituitary cell function

Abstract

Purine nucleosides and nucleotides are widely distributed substances that exhibit a diverse range of effects in a number of tissues, acting as important extracellular signalling molecules in addition to their more established roles in cellular metabolism. They mediate their effects via activation of distinct cell surface receptors, termed adenosine (or P1) and P2 purinergic receptors. Although roles for adenosine and adenine nucleotides have been described previously in the pituitary gland, the distribution of the receptor subtypes and the effects of their activation on pituitary function are not well defined. Recent evidence, however, has emerged to describe a complex signalling system for purines in the pituitary gland. Data from a variety of studies have shown that the expression pattern, number and affinity of adenosine and/or P2 receptors may be cell-type specific and that non-endocrine in addition to endocrine cells elaborate these receptors. These variations, along with the diverse range of signalling pathways activated, dictate the response of individual cell types to extracellular purines, with roles now emerging for these substances in the regulation of hormone release, pituitary cell proliferation and cytokine/growth factor expression. In this review, we discuss these advances and examine some implications for pituitary growth control and the response of the hypothalamic-pituitary-adrenal axis to stress and inflammation.

Intestinal Ischemia-Reperfusion Injury Alters Purinergic Receptor Expression in Clinically Relevant Extraintestinal Organs

“…Purinoceptors also serve to mediate changes in the expression of cellular adhesion molecules (40), and have been shown to modulate leukocyte-mediated reactive oxygen species release (41,42). Recently, nucleotides have been suggested to play a role in the hypothalamic-pituitaryadrenal axis during times of stress and inflammation (18), while purinoceptor-modulated acute and chronic inflammatory states have been known to occur for quite some time (19)(20)(21). Extracellular nucleotide receptor-mediated tissue injury and protection have been documented following ischemia-reperfusion in the lung (43), kidney (40,44,45), heart (24,46), and brain (47).…”

“…Purinoceptors are regionally localized, with subtype specificity and activity varying based upon relative agonist profiles and concentrations. Recently, nucleotides have been suggested to play a role in the hypothalamic-pituitary-adrenal axis during times of stress and inflammation (18). Additionally, nucleotides and their receptors modulate acute and chronic inflammatory states (19)(20)(21)(22), have been implicated in protection from ischemia-reperfusion injury (23)(24)(25), and participate in blood vessel autoregulation (26,27).…”

Purinergic signalling in endocrine organs

“…Adenosine increased release of IL-6 from primary anterior pituitary cell cultures [445] and the implications of this finding for inflammation and tumorigenesis were discussed [439]. Adenosine-induced IL-6 expression in FSC is mediated via A 2B receptors coupled to protein kinase (PK) C and p38 mitogen-activated protein kinase (MAPK) [440].…”

“…It has been claimed that adenosine increases interleukin (IL) 6 and decreases release of tumour necrosis factor from anterior pituitary cells [445]. Adenosine signalling pathways in the pituitary gland have been reviewed, highlighting the effects of adenosine on pituitary cell proliferation and the evidence for opposing actions on endocrine and FSC [438][439][440]. Briefly, A 1 receptors are expressed in rodent pituitary endocrine cell lines mediating hormone release, whereas A 2B receptors appear to be predominant in primary anterior pituitary cell cultures consisting mainly of FSC mediating stimulation of IL-6 secretion.…”

“…Adenosine is an important regulator of the functions of pituitary tumour GH4 cells, which secrete prolactin and growth hormone, by modulating, in an autocrine manner, the activity of L-type voltage-dependent calcium channels [439,612].…”